There are several techniques to determine CMC, e.g. fluorescence assays, light scattering, ultrasound absorption, conductivity, contact angle and surface tension or surface pressure measurements. The hydrophobocity of compounds is commonly determined by measuring their partition coefficient (log P) in an octanol/water two-phase system. Amphiphilicity and detergency properties have conventionally been determined by measuring the effect of the substance on the surface tension of water.
Phospholipidosis (PLD) is a known side effect caused by some pharmaceutical components and drugs. Phospholipids are accumulated in the cells, e.g. in the lungs, kidneys and the liver. Large amounts accumulated in the tissue compromise its normal, physiological function. Especially when a drug is taken for a long period of time the problem is enhanced, since greater amounts of phospholipids may accumulate in the cells. This can in turn lead to chronic, irreversible phospholipidosis and organ failure. This is a serious and expensive problem for the pharmaceutical industry, in particular if becoming evident after the launch of the drug so it has to be drawn back from the market.
Today there are two common ways of testing if a drug is causing PLD. One is to use cell cultures and a method to detect drug-induced changes in the cells. A disadvantage to this method, in addition to being labor-intensive, is that the reproducibility, particularly the between-laboratory reproducibility, in these assays tends to be poor. Likewise, cell cultures need constant care, and are susceptible to infections, variations in the growth conditions, and instabilities in cell lines due to genetic selection in extended culture.
The other option is to use animal tests. Both above methods are expensive and they can thus only be used late in the development process of the drug and neither is suited for large-scale screening of new drug compounds such as performed in lead optimization, for instance. There is thus a need for a test that reveals possible PLD inducing properties early in the development process, as the costs for developing a new drug rise exponentially towards the end of product development pipeline. Such a test would save both money and time in drug development as it would allow for the recognition and possible exclusion of potentially PLD causing compounds. Further this information can also be used for the improvement of compound chemistry so as to reduce its PLD inducing potential by proper adjustment of the compound physicochemistry.